The impetus for this proposal is derived from a broad interest in the biological functions of the serum complement system in man, both in health and disease. Major emphasis is placed on (a) the detection and characterization of hereditary deficiencies of complement components in man, utilizing both hemolytic titrations and immunodiffusion analyses for individual components; and (b) subsequent study of the effectiveness of these sera in supporting known functions of complement. A number of such human complement deficiency states have already been identified by the applicants, including two unique types (C5 and C6 deficiency). Patients with poorly explained acquired defects in the complement system will also be studied. Among the biological functions of complement to be analyzed in detail are: (1) a major study on interactions with human leukocytes, both polymorphonuclear and monomuclear, in phagocytosis and intracellular killing of various bacteria and yeasts, and in chemotaxis; (2) neutralization of enveloped and non-enveloped viruses; (3) production of ultrastructural lesions on cell membranes; (4) selected interactions with the clotting system; and (5) serum bactericidal activity.